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Vertebral Column > Haematopoiesis > Flashcards

Haematopoiesis Flashcards

1
Q

What is haematopoiesis?

A

Production of mature blood cells from pluripotent stem cells and haematopoietic stem cells

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2
Q

When does blood production begin?

A

Day 17 in embryo

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3
Q

Where does blood production begin in utero?

A

Extraembryonic splanchnic mesoderm surrounding yolk sac

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4
Q

What induces formation of haemangioblastic aggregates?

A

Mesoderm association with yolk sac

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5
Q

What cell lineages do haemangioblastic aggregates differentiate into?

A

Endothelial precursor cells

Primitive haematopoietic stem cells

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6
Q

What do the products of haemangioblastic aggregate differentiation form?

A

Blood islands

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7
Q

What do endothelial precursor cells differentiate into? Through what process do these cells form capillaries?

A

Endothelial cells

Vasculogenesis

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8
Q

How many waves do HSCs develop in?

A

2

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9
Q

From what does primitive hematopoiesis occur?

A

Mesodermal precursors which migrate to yolk sac

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10
Q

When does primitive hematopoiesis begin to make its productions?

A

Mid to late primitive streak stage

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11
Q

What cells does primitive haematopoiesis produce?

A

Primitive erythropoietic cells
Primitive macrophages
Primitive megakaryocytes

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12
Q

Describe primitive erythropoietic cells?

A

Nucleated
Contain embryonic Hb
6x larger than definitive RBCs

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13
Q

Describe primitive macrophages?

A

‘Mononuclear’ cell

Greater developmental potential

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14
Q

Describe primitive megakaryocytes?

A

Mature more rapidly

Contain less polyploidy

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15
Q

What is the cell potency of definitive HSCs?

A

Multipotent

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16
Q

Where do definitive HSCs arise?

A

A cluster of mesoderm cells which continue development in:

  • Placenta
  • Aorta-gonad-mesonephros region
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17
Q

Where can additional definitive HSCs arise?

A

Umbilical and vitelline arteries

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18
Q

One definitive HSCs have formed, where do they migrate to?

A

Foetal liver
Spleen
Bone marrow (just before birth)

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19
Q

From what do erythroblast progenitors develop from?

A

Common myeloid precursors

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20
Q

Where do primitive erythrocytes mature?

A

Bloodstream

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21
Q

How many generations are there between erythroid stem cells and erythrocytes?

A

At least 5

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22
Q

Where do definitive erythrocytes mature?

A

Foetal liver

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23
Q

Genes for what types of Hb are expressed by primitive erythrocytes?

A

Embryonic and adult haemoglobin

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24
Q

What is the difference between types of Hb?

A

Stability of subunit interference

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25
Q

What is the major site of production of all mature circulating blood in the adult?

A

Bone marrow

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26
Q

What is the exception to the main site of blood cell production?

A

T cells produced in thymus:

- Specialised microenvironment required to complete development

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27
Q

What did Samokhvalov et al., (2007) discover regarding haematopoiesis in adults?

A

Some adult HSCs have extraembryonic origin:

  • Migration of haematopoietic stem progenitors from yolk sac to fetal liver and thymus
  • Yolk-sac blood islands contain precursors to adult HSCs
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28
Q

What are true HSCs defined by?

A

Their capacity to long-term reconstitute the haematopoietic system of the adult

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29
Q

What do HSCs in the adult give rise to?

A

Differentiated progeny

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30
Q

Why do HSCs expand in the fetal liver?

A

To make up the number of HSCs necessary to sustain haematopoiesis throughout adulthood

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31
Q

Where do HSCs eventually migrate to and when?

A

Bone marrow cavities of the axial skeleton perinatally

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32
Q

Where can extramedullary erythropoiesis occur in the adult and under what conditions?

A

Liver or spleen

In severe bone marrow dysfunction

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33
Q

What did Schlitt et al., (1995) report in regards to extramedullary erythropoiesis?

A

Extramedullary erythropoiesis in the liver and multilineage haematopoiesis by donor-derived cells occurs following liver transplant in adult with normally functioning bone marrow

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34
Q

What type of tissue is bone marrow?

A

Primary lymphoid

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35
Q

Is bone marrow one of the biggest organs in the body?

A

Yes

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36
Q

Where is bone marrow found?

A

In the medullary cavity:

- Formed from interstices of cancellous bone

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37
Q

In what bones is bone marrow found?

A

Central parts of long bones

Some bones of axial skeleton

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38
Q

What are the three components of bone marrow?

A

Red marrow
Yellow marrow
Osseous

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39
Q

What parts of bone marrow are active and inactive?

A

Haematopoietically active = Red marrow

Inactive = Yellow marrow

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40
Q

What percentage of body weight does bone marrow constitute?

A

~5%

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41
Q

What is the entire bone marrow cavity in the neonate occupied by?

A

Proliferating haematopoietic cells

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42
Q

What happens to haematopoietic marrow as a child ages?

A

The regions is happens in contracts centripetally:

  • Can occur in phalanges in neonates
  • Contracts to only occur in more proximal bones
  • Replaced by fatty marrow
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43
Q

In what bones, specifically, does haematopoiesis occur in adults?

A 
Skull
Vertebrae
Ribs
Clavicles
Sternum
Pelvis
Proximal halves of:
- Humeri
- Femora
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44
Q

Can the volume of marrow cavities occupied with haematopoietic tissue increase with demand?

A

Yes

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45
Q

What is the stroma of bone marrow?

A 
Framework of:
- MSC-originated adipose cells
- Stromal cells
- Fibroblasts
- Macrophages
- Blood vessels
All interspersed within trabeculae
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46
Q

What is the parenchyma of bone marrow?

A

Spongy network of haematopoietic cells

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47
Q

How can the bone marrow within vertebral bodies be implicated in IV disc degeneration?

A

Vertebral bone marrow involved in IV disc nutrition

Fatty conversion reduces supply to IV disc

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48
Q

In what individuals is red marrow abundant in?

A

Neonates

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49
Q

What cells does red marrow contain?

A

Haematopoietic cells

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50
Q

Where is red marrow mainly localised?

A

Metaphyses of long bones

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51
Q

What marrow conversion occurs throughout childhood?

A

Red marrow to yellow marrow

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52
Q

Where does this marrow conversion occur and continue?

A

Starts in limbs
Continues proximally
Proceeds into axial skeleton

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53
Q

What are the components of red marrow?

A

40% water
40% fat
20% protein

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54
Q

What are the components of yellow marrow?

A

80% fat
15% water
5% protein

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55
Q

Where is yellow marrow found?

A

Appendicular skeleton of adults:

- Localised in diaphyses and epiphyses of long bones

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56
Q

What percentage of body fat does yellow marrow constitute?

A

~7%

57
Q

What are the functions of bone marrow adipocytes (and hence a function of yellow marrow)?

A

Storage
Secrete adiopokines:
- Leptin
- Adiponectin

58
Q

What cells share a common origin with bone marrow adipocytes? What is this origin? What does this common origin result in?

A 
Osteoblasts
Mesenchymal stem cells
Results in competition between alternative differentiation towards either:
- Adipogenesis OR
- Osteogenesis
59
Q

WHat HSCs are capable of self-renewal and what do they differentiate into?

A

Long-term HSCs

Differentiate into short-term HSCs

60
Q

What can short-term HSC differentiate into?

A

Common lymphoid progenitor

Common myeloid progenitor

61
Q

What do common myeloid progenitors differentiate into?

A

A common erythroid/megakaryocyte progenitor (MEP)

Granulocyte/macrophage progenitor (GMP) cells

62
Q

What is the life span of an erythrocyte/RBC?

A

~120 days

63
Q

How do RBCs appear?

A

Anucleated

Biconcave disc

64
Q

What is the main function of RBCs?

A

Gas exchanged:

  • Transport oxygen from lungs to tissues
  • Transport CO2 from tissues to lungs
65
Q

How do RBCs withstand shear during circulation?

A

Specialised membrane:

  • Has typical lipids, proteins and carbohydrates of a plasma membrane
  • Also has a cytoskeleton formed of cross-linked proteins
66
Q

How are old RBCs destroyed?

A

Spleen by trabecular arrangement
OR
Engulfed by macrophages

67
Q

What does the shape of a RBC allow?

A

Provides high flexibility for passages through small-diameter capillaries

68
Q

What are the general functions of leukocytes/WBCs?

A

Defend against pathogens
Remove:
- Damaged cells
- Toxins

69
Q

In terms of cells structure and contents, how do WBCs differ from RBCs generally?

A

WBCs are nucleated

WBCs contain other organelles

70
Q

What are the two groups of leukocytes?

A

Granulocytes

Agranulocytes

71
Q

What do both types of leukocytes contain?

A

Secretory vesicles

Lysosomes

72
Q

How are leukocytes classified into the two groups?

A

By what is visible under the light microscope

73
Q

What are the granulocytes?

A

Eosinophils
Neutrophils
Basophils

74
Q

What are the agranulocytes?

A

Monocytes

Lymphocytes

75
Q

What are the only type of WBC which are specific?

A

Lymphocytes

76
Q

Why are the other types of leukocytes non-specific?

A

They are activated by various stimuli

77
Q

How do eosinophils appear?

A

Bi-lobed nucleus

Granules stain bright red

78
Q

What are the functions of eosinophils?

A

Attack foreign bodies by releasing toxins (nitric oxide; cytotoxic enzymes)
Engulf:
- Smaller bacteria
- Cell debris
Also restrict the inflammatory actions of:
- Neutrophils
- Mast cells

79
Q

What colour do basophil granules stain?

A

Blue

80
Q

What do basophils contain?

A

Heparin

Histamines

81
Q

What are the functions of basophils?

A

Release heparin and histamines at injury site resulting in:

  • Vasodilatation
  • Prevention of blood clotting
82
Q

What cells are basophilic functions similar to?

A

Mast cells

83
Q

How do neutrophils appear?

A

Polymorphous nucleus
Many small granules
Larger granules

84
Q

What do the larger azurophilic granules in neutrophils contain?

A

Enzymes

85
Q

What is the life span of a neutrophil?

A

10 days

86
Q

What are the functions of neutrophils?

A

Engulf foreign material:
- Engulfed bacteria fused with lysosomes = Destruction
Release prostaglandins = Inflammation

87
Q

How do monocytes appear?

A

Kidney-shaped nuclei

Largest nucleocyte

88
Q

What is the life span of monocytes in the blood?

A

3 days

89
Q

Upon activation, what do monocytes develop into?

A

Macrophages

90
Q

What are the functions of activated monocytes (aka macrophages)?

A 
Phagocytose:
- Large cells
- Foreign objects
Release chemokines:
- Attract other WBCs to site of injury
91
Q

What are the least abundant WBCs?

A

Basophils

92
Q

What are the most abundant WBCs?

A

Neutrophils

93
Q

What are the most abundant agranulocytes?

A

Lymphocytes

94
Q

What are the general functions of lymphocytes?

A

Specific immune response to infection

Regulate inflammation

95
Q

What are the three types of lymphocytes?

A

T cells
B cells
NK cells

96
Q

What are the types of T cells and their functions?

A

Cytotoxic T cells - Attack foreign cells
Helper T cells - Activate B cells
Suppressor T cells - Inhibit T and B cell activity

97
Q

What do active B cells differentiate into and produce?

A

Plasma cells which produce and release antibodies

98
Q

What do NK cells do?

A

Recognise foreign cells
Attack by attaching onto target cells:
- Release vesicles which cover cell membrane
- Vesicles release perforin
- Perforin destroys foreign cell membrane

99
Q

From what do platelets originate?

A

As fragments of megakaryocytes after cell shearing during circulation

100
Q

What is the life span of a platelet?

A

10 days

101
Q

How does a platelet shape change after activation?

A

Changes from round discs to a sphere with dendritic extensions

102
Q

What are the functions of platelets?

A

Contain secretory granules:

- Secrete various proteins responsible for reinforcing platelet aggregation and platelet-surface coagulation reactions

103
Q

What is reconversion?

A

The reverse of the natural conversion process

The replacement of yellow marrow by haematopoietic cells

104
Q

What non-medical conditions can result in reconversion?

A

Cigarette smoking

Doing sports with a high oxygen debt

105
Q

What medical conditions can result in reconversion?

A

Obesity and related respiratory disorders
Diabetes
Chronic conditions related to asthma
Patients treated with haematopoietic growth factors

106
Q

When does reconversion occur?

A

When haematopoietic capacity of existing red marrow stores is exceeded

107
Q

What MRI features indicate reconversion?

A

Symmetry of changes
Changes do not extend beyond growth plate:
- Sparing articular ends of bones

108
Q

What did bone marrow biopsies in smokers show? (Poulton et al.)

A

Increased cellularity

Modest increase in maturo granulopoietic cells

109
Q

What is the potential explanation for reconversion in smokers?

A

Tissue hypoxia and increased carboxyhaemoglobin and resultant stimulation of erythrocyte production

110
Q

What are the limitations of the Poulton et al. study on reconversion in smokers?

A

Any red marrow in atypical locations was considered reconversion
Didn’t take into account that not all conversion may have occurred by age 25

111
Q

What is a neoplastic marrow infiltrate disorder?

A

Fatty marrow replaced with neoplastic tissue

112
Q

What neoplastic disease can infiltrate marrow?

A

Leukaemia
Lymphoma
Multiple myeloma
Metastatic disease

113
Q

Why do metastases more commonly localise in red marrow than yellow marrow?

A

Richer blood supply

114
Q

Where is the most common site of metastatic disease to the marrow?

A

Vertebral column (69%)

115
Q

What is a fibrotic marrow infiltrate disorder?

A

Fatty marrow replaced by fibrotic tissue

Infiltration occurs as a result of fibrosis

116
Q

What is osteomyelitis? What does it result in?

A

Infiltration of bone marrow by inflammatory cells
Results in:
- Increased extracellular water/fluid

117
Q

What is marrow infarction?

A

Obstruction of medulla

118
Q

What can result in marrow infarction?

A 
Malignant infiltration of marrow with consequent elevation of intraosseous pressure
OR
Secondary to:
- Chemotherapy
- Steroid injection
OR
Sickle cell disease
119
Q

What is the pathology of myeloid depletion?

A

Loss of normal red marrow:

  • Acellular or Hypocellular
  • Yellow marrow fills marrow space (fat and fibrosis)
120
Q

What are the pathological sequelae of myeloid depletion?

A

Oedema
Vascular congestion
Diminished haematopoiesis

121
Q

What can cause myeloid depletion?

A

Viral infections
Medications
Chemotherapy/Radiotherapy
Idiopathic/Unknown

122
Q

Within how many years of radiotherapy can the marrow recovery after myeloid depletion?

A

1-2 years

123
Q

What is myelofibrosis?

A

Replacement of normal marrow cells by fibrotic tissue

124
Q

What usually causes myelofibrosis?

A

Chemotherapy
Radiotherapy
Can be a primary disorder

125
Q

What is bone marrow hyperplasia?

A

The process of repopulation of yellow marrow by red marrow by reconversion mechanisms

126
Q

What causes bone marrow hyperplasia?

A

Increased demand for haematopoiesis

127
Q

Where does reconversion occur in bone marrow hyperplasia?

A

Begins in vertebrae and flat bones of pelvis
Progresses to long bones
(ie opposite pattern to physiological conversion with age)

128
Q

What are the causes of bone marrow hyperplasia (reconversion)?

A 
Severe chronic anaemia in:
- Sickle cell disease
- Thalassaemia
- Hereditary spherocytosis
Marrow replacement by neoplastic cells
Chemotherapy
Increased oxygen demands
129
Q

What cell lineages does bone marrow hyperplasia affect?

A

Can affect all lineages
OR
Just an individual cell line:
- Will affect myeloid/erythroid cell ratio

130
Q

What is hypoplasia?

A

Underdevelopment of a tissue of organ

131
Q

What is bone marrow hypoplasia?

A

Replacement of red marrow by yellow marrow by myeloid depletion mechanisms

132
Q

What can cause bone marrow hypoplasia?

A 
Typically chemotherapy/radiotherapy regimes
Also:
- Viral infections
- Other medications
- Unknown cause
133
Q

How does bone marrow hypoplasia progress?

A 
Initially bone marrow oedema
Decrease haematopoiesis
Finally red marrow replacement by:
- Adipose tissue
- Fibrosis
134
Q

What is thalassaemia?

A

Imbalanced globin chain production due to diminished or absent production of one or more globin chains

135
Q

What is the pathogenesis of thalassaemia?

A

Excess globin chains form tetramers and precipitate within RBCs:
- Leads to chronic haemolysis in bone marrow and peripheral blood

136
Q

What does the severity of thalassaemia depend on?

A

Type of mutation or deletion

137
Q

What are the subgroups of thalassaemia?

A

Alpha

Beta

138
Q

What process occurs in thalassaemia and why?

A

Extramedullary haematopoiesis

Due to chronic overproduction of erythrocytes

139
Q

How can thalassaemia affect the vertebral column? (Aydingoz et al., 1997)?

A

Thalassaemia results in extramedullary haematopoiesis
Extramedullary haematopoiesis results in hyperplasia of haematopoietic tissue
Spinal cord is compressed by epidural extramedullary haematopoietic tissue

Vertebral Column (14 decks)

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